Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an evolutionarily conserved motif and is sensitive to inositol hexakisphosphate

Colin Rickman; Deborah A Archer; Frederic A Meunier; Molly Craxton; Mitsunori Fukuda; Robert D Burgoyne; Bazbek Davletov

doi:10.1074/jbc.M310710200

Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an evolutionarily conserved motif and is sensitive to inositol hexakisphosphate

Colin Rickman, Deborah A Archer, Frederic A Meunier, Molly Craxton, Mitsunori Fukuda, Robert D Burgoyne, Bazbek Davletov

School of Engineering & Physical Sciences

Research output: Contribution to journal › Article › peer-review

106 Citations (Scopus)

Abstract

Synaptotagmins are membrane proteins that possess tandem C2 domains and play an important role in regulated membrane fusion in metazoan organisms. Here we show that both synaptotagmins I and II, the two major neuronal isoforms, can interact with the syntaxin/synaptosomal-associated protein of 25 kDa (SNAP-25) dimer, the immediate precursor of the soluble NSF attachment protein receptor (SNARE) fusion complex. A stretch of basic amino acids highly conserved throughout the animal kingdom is responsible for this calcium-independent interaction. Inositol hexakisphosphate modulates synaptotagmin coupling to the syntaxin/SNAP-25 dimer, which is mirrored by changes in chromaffin cell exocytosis. Our results shed new light on the functional importance of the conserved polybasic synaptotagmin motif, suggesting that synaptotagmin interacts with the t-SNARE dimer to up-regulate the probability of SNARE-mediated membrane fusion.

Original language	English
Pages (from-to)	12574-12579
Number of pages	6
Journal	Journal of Biological Chemistry
Volume	279
Issue number	13
DOIs	https://doi.org/10.1074/jbc.M310710200
Publication status	Published - 26 Mar 2004

Keywords

Amino Acid Motifs
Amino Acid Sequence
Animals
Brain
Calcium
Calcium-Binding Proteins
Catecholamines
Cell Membrane
Chromaffin Cells
Cloning, Molecular
Dimerization
Dose-Response Relationship, Drug
Evolution, Molecular
Exocytosis
Glutathione Transferase
HeLa Cells
Humans
Immunoblotting
Membrane Glycoproteins
Membrane Proteins
Microscopy, Confocal
Molecular Sequence Data
Nerve Tissue Proteins
Neurons
Phytic Acid
Precipitin Tests
Protein Binding
Protein Isoforms
Protein Structure, Tertiary
Qa-SNARE Proteins
RNA, Messenger
Rats
Recombinant Fusion Proteins
Reverse Transcriptase Polymerase Chain Reaction
Synaptosomal-Associated Protein 25
Synaptotagmins
Time Factors

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10.1074/jbc.M310710200

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title = "Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an evolutionarily conserved motif and is sensitive to inositol hexakisphosphate",

abstract = "Synaptotagmins are membrane proteins that possess tandem C2 domains and play an important role in regulated membrane fusion in metazoan organisms. Here we show that both synaptotagmins I and II, the two major neuronal isoforms, can interact with the syntaxin/synaptosomal-associated protein of 25 kDa (SNAP-25) dimer, the immediate precursor of the soluble NSF attachment protein receptor (SNARE) fusion complex. A stretch of basic amino acids highly conserved throughout the animal kingdom is responsible for this calcium-independent interaction. Inositol hexakisphosphate modulates synaptotagmin coupling to the syntaxin/SNAP-25 dimer, which is mirrored by changes in chromaffin cell exocytosis. Our results shed new light on the functional importance of the conserved polybasic synaptotagmin motif, suggesting that synaptotagmin interacts with the t-SNARE dimer to up-regulate the probability of SNARE-mediated membrane fusion.",

keywords = "Amino Acid Motifs, Amino Acid Sequence, Animals, Brain, Calcium, Calcium-Binding Proteins, Catecholamines, Cell Membrane, Chromaffin Cells, Cloning, Molecular, Dimerization, Dose-Response Relationship, Drug, Evolution, Molecular, Exocytosis, Glutathione Transferase, HeLa Cells, Humans, Immunoblotting, Membrane Glycoproteins, Membrane Proteins, Microscopy, Confocal, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Phytic Acid, Precipitin Tests, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, Qa-SNARE Proteins, RNA, Messenger, Rats, Recombinant Fusion Proteins, Reverse Transcriptase Polymerase Chain Reaction, Synaptosomal-Associated Protein 25, Synaptotagmins, Time Factors",

author = "Colin Rickman and Archer, {Deborah A} and Meunier, {Frederic A} and Molly Craxton and Mitsunori Fukuda and Burgoyne, {Robert D} and Bazbek Davletov",

year = "2004",

month = mar,

day = "26",

doi = "10.1074/jbc.M310710200",

language = "English",

volume = "279",

pages = "12574--12579",

journal = "Journal of Biological Chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology Inc.",

number = "13",

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TY - JOUR

T1 - Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an evolutionarily conserved motif and is sensitive to inositol hexakisphosphate

AU - Rickman, Colin

AU - Archer, Deborah A

AU - Meunier, Frederic A

AU - Craxton, Molly

AU - Fukuda, Mitsunori

AU - Burgoyne, Robert D

AU - Davletov, Bazbek

PY - 2004/3/26

Y1 - 2004/3/26

N2 - Synaptotagmins are membrane proteins that possess tandem C2 domains and play an important role in regulated membrane fusion in metazoan organisms. Here we show that both synaptotagmins I and II, the two major neuronal isoforms, can interact with the syntaxin/synaptosomal-associated protein of 25 kDa (SNAP-25) dimer, the immediate precursor of the soluble NSF attachment protein receptor (SNARE) fusion complex. A stretch of basic amino acids highly conserved throughout the animal kingdom is responsible for this calcium-independent interaction. Inositol hexakisphosphate modulates synaptotagmin coupling to the syntaxin/SNAP-25 dimer, which is mirrored by changes in chromaffin cell exocytosis. Our results shed new light on the functional importance of the conserved polybasic synaptotagmin motif, suggesting that synaptotagmin interacts with the t-SNARE dimer to up-regulate the probability of SNARE-mediated membrane fusion.

AB - Synaptotagmins are membrane proteins that possess tandem C2 domains and play an important role in regulated membrane fusion in metazoan organisms. Here we show that both synaptotagmins I and II, the two major neuronal isoforms, can interact with the syntaxin/synaptosomal-associated protein of 25 kDa (SNAP-25) dimer, the immediate precursor of the soluble NSF attachment protein receptor (SNARE) fusion complex. A stretch of basic amino acids highly conserved throughout the animal kingdom is responsible for this calcium-independent interaction. Inositol hexakisphosphate modulates synaptotagmin coupling to the syntaxin/SNAP-25 dimer, which is mirrored by changes in chromaffin cell exocytosis. Our results shed new light on the functional importance of the conserved polybasic synaptotagmin motif, suggesting that synaptotagmin interacts with the t-SNARE dimer to up-regulate the probability of SNARE-mediated membrane fusion.

KW - Amino Acid Motifs

KW - Amino Acid Sequence

KW - Animals

KW - Brain

KW - Calcium

KW - Calcium-Binding Proteins

KW - Catecholamines

KW - Cell Membrane

KW - Chromaffin Cells

KW - Cloning, Molecular

KW - Dimerization

KW - Dose-Response Relationship, Drug

KW - Evolution, Molecular

KW - Exocytosis

KW - Glutathione Transferase

KW - HeLa Cells

KW - Humans

KW - Immunoblotting

KW - Membrane Glycoproteins

KW - Membrane Proteins

KW - Microscopy, Confocal

KW - Molecular Sequence Data

KW - Nerve Tissue Proteins

KW - Neurons

KW - Phytic Acid

KW - Precipitin Tests

KW - Protein Binding

KW - Protein Isoforms

KW - Protein Structure, Tertiary

KW - Qa-SNARE Proteins

KW - RNA, Messenger

KW - Rats

KW - Recombinant Fusion Proteins

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Synaptosomal-Associated Protein 25

KW - Synaptotagmins

KW - Time Factors

U2 - 10.1074/jbc.M310710200

DO - 10.1074/jbc.M310710200

M3 - Article

C2 - 14709554

SN - 0021-9258

VL - 279

SP - 12574

EP - 12579

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 13

ER -

Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an evolutionarily conserved motif and is sensitive to inositol hexakisphosphate

Abstract

Keywords

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